Dynamic modulation of adhesion GPCR function through complex formation (B06)

• Subject Area: Biochemistry ; Pharmacology ; Cell Biology
• Term: since 2020
• Project identifier: Deutsche Forschungsgemeinschaft (DFG) - Project number 421152132

Adhesion GPCR (aGPCR) use unusual molecular strategies to modulate the physiological functions of the expressing and neighboring cells. Our recent work demonstrated that aGPCR isoforms form homo and heteromeric assemblies to tune cellular mechanoresponsiveness. Building on this finding, we now aim to identify the molecular interfaces that enable complex formation and explore the molecular mechanisms that underlie their activity and signaling facility. In this context, we will investigate if and how the newly identified ligand TLR 8 (toll-like receptor 8, Tollo) is involved and how cell autonomy of this aGPCR-ligand pair is organized. Moreover, we intend to decipher the function of additional aGPCR-ligand pairs in vivo in their native cellular context. For these purposes, we will generate a FRET-based toolkit of intra and intermolecular aGPCR and non-GPCR sensors, use established signaling assays and proteinbiochemical protocols in combination with a series of in vivo readouts including Ca2+ imaging and electrophysiology.

• DFG Programme: Collaborative Research Centres
• Subproject of: SFB 1423: Structural Dynamics of GPCR Activation and Signaling
• Applicant Institution: Universität Leipzig
• Project Heads: Professor Dr. Tobias Langenhan; Dr. Nicole Scholz